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Biomedical subjects

F Barkhof

Publications and source records attributed to F Barkhof.

At least 199 records · Page 11Linked to original sources

The functional basis of ocular dominance: functional MRI (fMRI) findings.

Changes in cortical metabolism and cerebral perfusion may be recorded non-invasively with functional magnetic resonance imaging (fMRI). In pilot experiments, using fMRI with photic stimulation, we found differences between activated areas when the left or the right eye was stimulated separately. In this study we investigated whether this could be explained by ocular dominance. We studied 26 healthy volunteers (mean age 23.3 +/- 3.5 years). Ocular dominance was determined by means of the near-far alignment test. fMRI-measurements consisted of a double-slice gradient echo sequence. Slices were acquired placed parallel on either side of the calcarine fissure. Visual stimulation was done with goggles with two LED matrices (red light, 8 Hz); each in front of one eye. In each subject, the left and right eye were stimulated separately and together, in a randomly alternating order. Twenty-two subjects showed activation, of whom eight subjects had a dominant left eye and 14 a dominant right eye. In general the size of the activated area was bigger upon stimulation of the dominant eye. The difference with the area upon stimulation of the non-dominant eye was statistically significant in the right eye dominant group. These results indicate that the dominant eye actually activates a larger area of the primary visual cortex than the non-dominant eye. This provides for the first time a functional basis for the concept of ocular dominance.

Adult↗

Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. US National MS Society Task Force.

Because of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRI) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing-remitting and secondary progressive MS, monthly T2-weighted and gadolinium-enhanced brain MRI is an excellent tool for short-term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6- to 12-month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N-acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1-weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.

Clinical Trials as Topic↗

Comparison of film-screen combination and digital fluorography in gastrointestinal barium examinations in a clinical setting.

OBJECTIVE: Digital fluoroscopy systems have been developed for gastrointestinal barium studies. We compare the performance of a commercially available digital fluoroscopy system with conventional film-screen combinations in gastrointestinal barium studies. METHODS: Two consecutive groups of outpatients underwent diagnostic barium examinations of esophagus, stomach, or colon using either a film-screen technique (n = 32) or a digital fluoroscopy system with an 8-bit gray scale (n = 31). A standardized biphasic protocol was employed in all patients by the same set of investigators and scored subjectively for contrast performance in single-contrast and double-contrast mode and for spatial resolution. RESULTS: For the whole group there were no significant differences between the two techniques. In the subgroup of esophagus studies, digital fluoroscopy performed better during the full-column part of the examination. In the subgroup of colon studies, the film-screen technique performed better during the double-contrast part of the examination. To reach sufficient spatial resolution with the digital system (884(2) matrix), the smallest input screen had to be used (23 cm), resulting in a higher number of exposures than with the film-screen combination (P = 0.006). The average amount of film used was not significantly different. CONCLUSION: In a clinical setting the contrast performance and spatial resolution of digital fluoroscopy systems can be comparable with conventional film-screen combinations.

Barium Sulfate↗

Disappearance of multiple sclerosis lesions with severely prolonged T1 on images obtained by a FLAIR pulse sequence.

Although the superiority of FLAIR over conventional T2-weighted spin-echo (SE) is still unclear, one potential advantage would be its use in quantitative lesion load measurements. We have observed a potential pitfall regarding the use of FLAIR in image quantification. We report a case where a part of the hyperintense lesions on T2 SE, which was hypointense on T1 SE, subsequently was found to be isointense to brain on FLAIR images. Therefore, quantification of lesion load by means of FLAIR might underestimate the "true" lesion load, as seen on T2 SE.

Brain↗

Normal gyration and sulcation in preterm and term neonates: appearance on MR images.

PURPOSE: To provide a practical standard for normal development of gyri and sulci in preterm and term neonates. MATERIALS AND METHODS: Thirty-nine living preterm infants without substantial neurologic problems underwent magnetic resonance (MR) imaging of the brain. Five infants who were born at term but died of a nonneurologic disorder within 1 week and who underwent autopsy were examined after death with MR imaging. Seven cerebral surface areas were defined, and the development of gyri and sulci in each area was assigned a score between 1 and 5. RESULTS: The postconceptional age (PCA) range of the newborns was 30-42 weeks. When the gyral development scores were assessed as a function of PCA, four transition points could be discerned for the brain as a whole; these transitions occurred at PCAs of 32, 34, 37, and 40 1/2-41 weeks. These four transition points allowed the general gyral development to be divided into five stages. Development of gyri and sulci was most advanced in the area of the central sulcus and the medical occipital area. Development was latest in the frontobasal and frontopolar areas and the anterior part of the temporal lobe. CONCLUSION: A simple staging system allows easy assessment of the progress of cerebral gyration and sulcation in preterm and term infants.

Brain↗

Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts.

Cerebral atrophy (CA) in stroke patients is associated with poststroke dementia and may reflect underlying neurodegenerative pathology. Therefore, regional CA may be valuable to study in patients who develop poststroke dementia. The aim of this study was to test the reproducibility of a qualitative rating scale of CA on MRI. MRI scans were performed in 50 consecutive patients (age range 19-81) admitted for an acute hemispheric ischemic stroke. CA was assessed on 2 occasions 24 h apart, on axial T2-weighted sequences by 4 independent observers. We evaluated CA in 13 regions on a 0-3 scale. The sum of the subscores was called the CA score (range: 0-39). The level of agreement was expressed by kappa statistics as well as by analysis of variance for interexaminer reproducibility studies. The mean CA scores ranged from 2.8 to 11.0, indicating the low prevalence of CA in this sample. Complete agreement was reached in 41.7% during the first assessment and in 44.1% in the second assessment. The interobserver agreement was moderate in the first session (mean overall kappa: 0.48) and substantial in the second (mean overall kappa: 0.67). The intraobserver agreement was good for all raters (mean kappa: 0.65). Standardized to the range of the scale, standard deviations of the differences between CA scores of the 4 raters in the 2 sessions were 11.1 and 11.2%; within raters it was 4.4%. We conclude that the assessment of CA using this rating scale is possible in stroke patients. It provides regional atrophy measurements and is reproducible when performed by 1 rater.

Adult↗

Methylprednisolone treatment in multiple sclerosis: effect of treatment, pharmacokinetics, future.

High dose intravenous methylprednisolone treatment is effective and safe in the treatment of relapses in multiple sclerosis, but the long term effects are unclear. Pharmacokinetics are almost unknown, but may be very important for the understanding of the clinical and paraclinical effects. In view of what is known now, IVMP should have a prominent place in basic and clinical MS research.

Dose-Response Relationship, Drug↗

A phase II trial of anti-CD4 antibodies in the treatment of multiple sclerosis.

In multiple sclerosis (MS) myelin damage is the result of a chronic inflammatory process mediated by CD4 positive T helper/effector cells. In experimental allergic encephalomyelitis (EAE), the animal model of MS, treatment with anti-CD4 antibodies can prevent the onset of disease. Natural history studies have demonstrated that gadolinium enhanced magnetic resonance imaging (MRI) of the brain is more sensitive and objective in assessing inflammatory disease activity in MS than clinical monitoring, so that less patients and shorter studies suffice to reach the same statistical power as compared to trials using clinical outcome parameters. In this paper we describe the design of an exploratory trial of chimeric monoclonal anti-CD4 antibodies in the treatment of MS. For this study we chose the number of active MS lesions on monthly gadolinium enhanced MRI scans as the primary outcome measure.

Adolescent↗

Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis.

MRI findings are increasingly used as outcome measures in therapeutic trials in MS. The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T1-weighted spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.

Adult↗

Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2.

There is evidence that treatment with an antibody to tumor necrosis factor alpha (TNF alpha) improves an animal model of multiple sclerosis (MS) and is beneficial in two systemic inflammatory disease in humans, but there are no reports about anti-TNF treatment of MS. Therefore, we treated two rapidly progressive MS patients with intravenous infusions of a humanized mouse monoclonal anti-TNF antibody (cA2) in an open-label phase I safety trial and monitored their clinical status, gadolinium-enhanced brain magnetic resonance imaging (MRI), and peripheral blood and cerebrospinal fluid (CSF) immunologic status. We did not notice any clinically significant neurologic changes in either patient. The number of gadolinium-enhancing lesions increased transiently after each treatment in both patients. CSF leukocyte counts and IgG index increased after each treatment. The transient increase in the number of gadolinium-enhancing lesions that followed each infusion of cA2 together with the increase in cells and immunoglobulin in the CSF of each patient suggest that the treatment caused immune activation and an increase in disease activity. These results suggest that further use of cA2 in MS is not warranted and that studies of other agents that antagonize TNF alpha should be carried out with frequent monitoring of gadolinium-enhanced MRIs.

Adult↗

Comparison of two MR sequences for the detection of multiple sclerosis lesions in the spinal cord.

PURPOSE: To compare cardiac-triggered dual-echo spin-echo and magnetization transfer-prepared gradient-echo (MT-GE) MR imaging in the detection of multiple sclerosis (MS) lesions in the spinal cord. METHODS: The cervical spinal cord in 20 patients with MS and in nine healthy volunteers was examined with spin-echo and MT-GE MR imaging. Sagittal images were scored for number of lesions, certainty about lesions, image quality, and visual hindrance by artifacts in random order by two radiologists separately and in a blinded manner. RESULTS: In one healthy volunteer, a lesion was seen on images obtained with both images. Lesion/cord contrast-to-noise ratio was equal on both the MT-GE and T2-weighted spin-echo images. MT-GE images showed better image quality and fewer artifacts than the spin-echo images did. The readers found approximately the same number of lesions. However, the number of definite lesions was higher for the spin-echo sequence than for the MT-GE sequence. One reader found 45 definite lesions with spin-echo and 34 definite lesions with MT-GE. For the other reader, these numbers were 37 (spin-echo) and 31 (MT-GE). On the spin-echo images, 90% of the patients were considered to have definite lesions; on the MT-GE images, the readers found definite lesions in 65% (reader 1) and in 70% (reader 2) of the patients. CONCLUSION: Image quality was better with the MT-GE technique than with the spin-echo technique, and lesion/cord contrast-to-noise ratio on the MT-GE images was equal to that of T2-weighted spin-echo images. However, for detecting spinal cord MS lesions in the sagittal plane, the spin-echo images were preferred to the MT-GE images.

Adult↗

Magnetic resonance imaging of epilepsy in multiple sclerosis: a case control study. Implications for treatment trials with 4-aminopyridine.

A case-control study of epilepsy in multiple sclerosis (MS) is presented using magnetic resonance (MR) imaging to semiquantitatively assess cortical-subcortical lesion load. In this sample of 13 pairs of cases with MS and epilepsy and controls with MS without epilepsy we found statistically higher cumulated cortical-subcortical lesion loads in the cases than in the controls (Wilcoxon, P = 0.036). Total lesion loads (cortical-subcortical plus deep white matter loads) did not differ significantly (P > 0.1) between cases and controls. The relative risk for seizures as determined by the odds ratio of a cortical-subcortical lesion load of > or = 20 was 8.8 (chi 2 = 5.23, P 0.025), the odds ratio of a large (> 1 cm) cortico-subcortical lesion was 4.7 (chi 2 = 4.9, P < 0.05), while the 2 MR criteria combined show an odds ratio of 19.2 (chi 2 = 8.0, P < 0.005). We conclude that: first, the presence of cortical-subcortical lesions in part accounts for the occurrence of seizures in MS patients; second, due to the substantial overlap of MR imaging scores between cases and controls the ultimate use of these MR imaging findings in the management of individual patients or in the organizations of trials should depend on the expected benefit of the treatment. If the benefit is only moderate or not known a cautious approach with exclusion of cases showing a substantial cortical-subcortical lesion load on MR imaging seems appropriate in trials with drugs, like 4-aminopyridine, that lower the epileptic threshold.

4-Aminopyridine↗

Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging: interobserver reliability.

We conducted an interobserver study to assess agreement on visual rating of medial temporal lobe atrophy on coronal T1-weighted MRI. A total of 100 studies of elderly individuals, using two different MRI techniques (spin echo and inversion recovery sequences), were analysed by four raters (three neurologists and one neuroradiologist) using a five-point rating scale. Complete agreement was found in 37% of the total sample. Interobserver agreement as expressed by kappa values was 0.44 (95% CI = 0.34-0.54) and 0.51 (95% CI = 0.41-0.61) for the two techniques. After dichotomizing medial temporal lobe atrophy into present or absent, a post hoc analysis revealed higher complete agreement (70%), with kappa values of 0.59 (95% CI = 0.51-0.67) and 0.62 (95% CI = 0.48-0.075), for the two techniques (all four raters). From this study we conclude that visual rating of medial temporal lobe atrophy on MRI in the coronal plane yields fair to good agreement among observers. We recommend this type of visual rating for use in clinical settings when a quick judgement on the presence of medial temporal lobe atrophy is needed.

Atrophy↗

Partially saturated fluid attenuated inversion recovery (FLAIR) sequences in multiple sclerosis: comparison with fully relaxed FLAIR and conventional spin-echo.

Fluid attenuated inversion recovery (FLAIR) sequences produce selective cerebrospinal fluid (CSF) suppression by employing a very long inversion time (TI). We used the FLAIR sequence to study patients with multiple sclerosis (MS) at 0.6 T. So far, a very long TR (and long acquisition time) has been used in a fully relaxed (FR-FLAIR) system. To speed up the FLAIR sequences, we used a shorter TR, and demonstrated that complete CSF suppression can be maintained with partial saturation (PS-FLAIR) by reducing TI at the same time. The introduction of partial saturation, however, reduced the contrast between lesions and normal appearing white matter (NAWM). Suboptimal CSF suppression therefore had to be accepted to maintain sufficient lesion to NAWM contrast. Using a TE of 60 ms, the PS-FLAIR and FR-FLAIR performed equally well in the detection of MS-lesions, although the former provided poorer CSF suppression. Both FLAIR sequences, however, provided poorer constrast between lesions and NAWM compared to conventional spin-echo sequences. Although the long acquisition time of the FLAIR sequence can be reduced by using partial saturation, complete CSF suppression and good lesion to NAWM contrast are incompatible at short TRs. Using a TE of 60 ms, conventional spin-echo sequences detect more lesions and provide better contrast between lesions and NAWM than FLAIR sequences in MS patients.

Brain↗

Quantitative assessment of MRI lesion load in monitoring the evolution of multiple sclerosis.

In recent years, several segmentation techniques have been developed to quantify brain MRI lesion load in multiple sclerosis and are now being used increasingly for both evaluating the natural history of the disease and monitoring the efficacy of treatment. Such techniques have been applied extensively to conventional T2-weighted images; there is less experience to date with gadolinium-enhanced scans and newer MR parameters which are thought to reflect the more destructive aspects of the pathological process. Manual outlining of lesions on T2-weighted images is moderately accurate when performed by an experienced observer and has been validated in large clinical trials, but is very time consuming. Semi-automated intensity-based techniques appear to be more reproducible, but are still slow to perform. Faster techniques with higher reproducibility are still needed. The correlations between conventional T2 lesion load and clinical outcome is strong in patients seen at first presentation with clinically isolated syndromes suggestive of multiple sclerosis, but much weaker in established multiple sclerosis. The application of quantitative assessment of the MR parameters which are more specific for the disabling aspects of the pathological process (i.e. demyelination, axonal loss and spinal cord involvement) may improve the correlation with clinical status.

Brain↗

Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a follow-up study.

We obtained two conventional unenhanced T2-weighted brain MRI scans, separated by an interval of 24 to 36 months, in 281 patients with multiple sclerosis (MS). At the time of each scan, clinical disability was rated using the Kurtzke Expanded Disability Status Scale (EDSS). Changes in disability between the two examinations correlated weakly but significantly with the number of new (Spearman's rank correlation coefficient = 0.13; p = 0.02) and enlarging (Spearman's rank correlation coefficient = 0.18; p = 0.002) MRI lesions. This result suggests that brain T2-weighted MRI is a useful supplementary marker of disease activity in definitive (phase III) clinical treatment trials in MS.

Adult↗

Medial temporal lobe atrophy in an open population of very old persons: cognitive, brain atrophy, and sociomedical correlates.

Medial temporal lobe structures may be important for memory. We examined the cognitive, brain atrophy, and sociomedical correlates of medial temporal lobe atrophy (MTA) in 59 individuals (79.2 +/- 4.6 years old) randomly selected from a population-based study within strata of age and severity of clinically assessed DSM-III-R dementia (45 clinically normal and 14 mild/severely demented). MTA was qualitatively assessed on coronal T-1-weighted MRI. Thirty-three percent of the sample showed MTA, which was associated with dementia severity (p < 0.01), and cortical and white matter atrophy. MTA was not associated with age, education, sex, depressive symptoms, or presence of infarction. Controlling for age, education, and associated brain atrophy, those with MTA performed more poorly on a general test of cognitive function (the neuropsychological test component of the Cambridge Examination for Mental Disorders of the Elderly; p < 0.04) and its subtests of memory function (p < 0.02) and memory-related functions, including perception, fluency, and orientation (p < 0.05). In the clinically normal subsample, those with MTA performed more poorly on the memory function (p < 0.05) subtests. We conclude that MTA is common among very old persons, is associated with other brain abnormalities implicated in cognitive function, but may specifically contribute to memory dysfunction in the general population of very old persons.

Aged↗

Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging.

We investigated the histopathologic correlates of white matter changes in Alzheimer's disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRI. White matter changes were rated on a 0 to 3 scale in 51 regions. Histopathologically, we subjectively rated the loss of myelinated axons in the deep and periventricular white matter, denudation of the ventricular ependyma, gliosis, width of the perivascular spaces, and leptomeningeal congophilic angiopathy; we measured structural changes in the walls of the blood vessels in the white matter in micrometers. The AD brains displayed significantly more white matter hyperintensities on MRI than controls. Histopathologically, the denudation of the ventricular ependyma and the gliosis were significantly more severe in AD than in controls, and there was a trend toward more loss of myelinated axons in the deep white matter in the AD brains (p = 0.07). The MRI abnormalities correlated with the loss of myelinated axons in the deep white matter (r' = 0.37; p < 0.01) and with the denudation of the ventricular lining (r' = 0.54; p < 0.01). We could not find any evidence for arteriolosclerosis, but the mean thickness of the adventitia of the arteries of the deep white matter in AD almost doubled the value in control brains (p = 0.0009). We conclude that white matter abnormalities in AD patients and controls consist of loss of myelinated axons, probably caused by arterial changes and breakdown of the ventricular lining. Since imaging/histopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.

Aged↗